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However, the relationships among CAG expansions, death of specific cell types and molecular events associated with these processes are not established. Here, we used fluorescence-activated nuclear sorting (FANS) and deep molecular profiling to gain insight into the properties of cell types of the human striatum and cerebellum in HD and control donors. CAG expansions arise at\n                    <jats:italic>mHTT<\/jats:italic>\n                    in striatal medium spiny neurons (MSNs), cholinergic interneurons and cerebellar Purkinje neurons, and at mutant\n                    <jats:italic>ATXN3<\/jats:italic>\n                    in MSNs from SCA3 donors. CAG expansions in MSNs are associated with higher levels of MSH2 and MSH3 (forming MutS\u03b2), which can inhibit nucleolytic excision of CAG slip-outs by FAN1. Our data support a model in which CAG expansions are necessary but may not be sufficient for cell death and identify transcriptional changes associated with somatic CAG expansions and striatal toxicity.\n                  <\/jats:p>","DOI":"10.1038\/s41588-024-01653-6","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T06:02:18Z","timestamp":1706594538000},"page":"383-394","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":169,"title":["Cell-type-specific CAG repeat expansions and toxicity of mutant Huntingtin in human striatum and cerebellum"],"prefix":"10.1038","volume":"56","author":[{"given":"Kert","family":"M\u00e4tlik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Baffuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit Laxmikant","family":"Deshmukh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Caron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-7169","authenticated-orcid":false,"given":"Jean-Yves","family":"Masson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9545-4205","authenticated-orcid":false,"given":"Christopher E.","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-8704","authenticated-orcid":false,"given":"Nathaniel","family":"Heintz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"1653_CR1","doi-asserted-by":"publisher","first-page":"R254","DOI":"10.1093\/hmg\/ddab170","volume":"30","author":"JF Gusella","year":"2021","unstructured":"Gusella, J. 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